Electrical Stimulation: How It Works and How to Apply It.

Electrical stimulation is emerging as a perioperative strategy to improve peripheral nerve regeneration and enhance functional recovery. Despite decades of research, new insights into the complex multifaceted mechanisms of electrical stimulation continue to emerge, providing greater understanding of the neurophysiology of nerve regeneration. In this study, we summarize what is known about how electrical stimulation modulates the molecular cascades and cellular responses innate to nerve injury and repair, and the consequential effects on axonal growth and plasticity. Further, we discuss how electrical stimulation is delivered in preclinical and clinical studies and identify knowledge gaps that may provide opportunities for optimization.

Geographic variation in breast reconstruction surgery after mastectomy for females with breast cancer in Alberta, Canada.

BACKGROUND: Breast cancer is the most common cancer affecting females in Canada, and about half of females with breast cancer are treated with mastectomy. We sought to evaluate geographic variation in breast reconstruction surgery in Alberta, Canada. METHODS: Using linked population-based administrative databases, we extracted data on all Alberta females aged 18 years and older who were diagnosed with breast cancer and treated with mastectomy during 2004-2017. Analyses included regression modelling of odds of reconstruction at 1 year and a spatial scan to identify geographic clusters of lower numbers of reconstruction. RESULTS: A total of 16 198 females diagnosed with breast cancer were treated with a mastectomy, and 1932 (11.9%) had reconstruction within 1 year postmastectomy. Those with reconstruction were more likely to be younger (adjusted odds ratio [OR] 16.7, 95% confidence interval [CI] 13.7-20.3; aged 21-44 yr v. ≥ 65 yr) and were less likely to be from lower-income neighbourhoods. They were more likely to have at least 1 comorbidity and were more likely to have advanced stages of cancer and to require chemotherapy (adjusted OR 0.55, 95% CI 0.47-0.65) or radiotherapy after mastectomy (adjusted OR 0.59, 95% CI 0.39-0.87) than females without reconstruction. We identified rural northern and southeastern clusters with frequencies of reconstruction that were 69.6% and 41.6% of what was expected, respectively. CONCLUSION: We found an overall postmastectomy rate of breast reconstruction of 11.9%, and we identified geographic variation. Predictors of reconstruction in Alberta were similar to those previously described in the literature, specifically with patients in rural communities having lower rates of reconstruction than their urban counterparts. These results suggest that further interventions are required to identify the specific barriers to reconstruction within rural communities and to create strategies to ensure equitable access to all residents.

'Inlay' Regenerative Peripheral Nerve Interface (RPNI) is superior to 'Burrito' RPNI for successful treatment of rat neuroma pain.

SUMMARY: Treatment of painful neuromas has long posed a significant challenge for peripheral nerve patients. The Regenerative Peripheral Nerve Interface (RPNI) provides the transected nerve with a muscle graft target to prevent neuroma formation. Discrepancies in the RPNI surgical techniques between animal models (Inlay-RPNI) versus clinical studies (Burrito-RPNI) preclude direct translation of results from bench to bedside and may account for variabilities in patient outcomes. We compared outcomes of these two surgical techniques in a rodent model. Animals treated with the Burrito-RPNI after tibial nerve neuroma formation demonstrated no improvement in pain assessment, and tissue analysis revealed complete atrophy of the muscle graft with neuroma recurrence. By contrast, animals treated with the Inlay-RPNI had significant improvements in pain with viable muscle grafts. Our results suggest superiority of the Inlay-RPNI surgical technique for the management of painful neuroma in rodents.

A Direct Comparison of Targeted Muscle Reinnervation and Regenerative Peripheral Nerve Interfaces to Prevent Neuroma Pain.

BACKGROUND AND OBJECTIVES: Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) surgeries manage neuroma pain; however, there remains considerable discord regarding the best treatment strategy. We provide a direct comparison of TMR and RPNI surgery using a rodent model for the treatment of neuroma pain. METHODS: The tibial nerve of 36 Fischer rats was transected and secured to the dermis to promote neuroma formation. Pain was assessed using mechanical stimulation at the neuroma site (direct pain) and von Frey analysis at the footpad (to assess tactile allodynia from collateral innervation). Once painful neuromas were detected 6 weeks later, animals were randomized to experimental groups: (a) TMR to the motor branch to biceps femoris, (b) RPNI with an extensor digitorum longus graft, (c) neuroma excision, and (d) neuroma in situ. The TMR/RPNIs were harvested to confirm muscle reinnervation, and the sensory ganglia and nerves were harvested to assess markers of regeneration, pain, and inflammation. RESULTS: Ten weeks post-TMR/RPNI surgery, animals had decreased pain scores compared with controls ( P < .001) and they both demonstrated neuromuscular junction reinnervation. Compared with neuroma controls, immunohistochemistry showed that sensory neuronal cell bodies of TMR and RPNI showed a decrease in regeneration markers phosphorylated cyclic AMP receptor binding protein and activation transcription factor 3 and pain markers transient receptor potential vanilloid 1 and neuropeptide Y ( P < .05). The nerve and dorsal root ganglion maintained elevated Iba-1 expression in all cohorts. CONCLUSION: RPNI and TMR improved pain scores after neuroma resection suggesting both may be clinically feasible techniques for improving outcomes for patients with nerve injuries or those undergoing amputation.

Current Concepts in the Management of Primary Lymphedema.

Primary lymphedema is a heterogeneous group of conditions encompassing all lymphatic anomalies that result in lymphatic swelling. Primary lymphedema can be difficult to diagnose, and diagnosis is often delayed. As opposed to secondary lymphedema, primary lymphedema has an unpredictable disease course, often progressing more slowly. Primary lymphedema can be associated with various genetic syndromes or can be idiopathic. Diagnosis is often clinical, although imaging can be a helpful adjunct. The literature on treating primary lymphedema is limited, and treatment algorithms are largely based on practice patterns for secondary lymphedema. The mainstay of treatment focuses on complete decongestive therapy, including manual lymphatic drainage and compression therapy. For those who fail conservative treatment, surgical treatment can be an option. Microsurgical techniques have shown promise in primary lymphedema, with both lymphovenous bypass and vascularized lymph node transfers demonstrating improved clinical outcomes in a few studies.

The Effect of Electrical Stimulation on Nerve Regeneration Following Peripheral Nerve Injury.

Peripheral nerve injuries (PNI) are common and often result in lifelong disability. The peripheral nervous system has an inherent ability to regenerate following injury, yet complete functional recovery is rare. Despite advances in the diagnosis and repair of PNIs, many patients suffer from chronic pain, and sensory and motor dysfunction. One promising surgical adjunct is the application of intraoperative electrical stimulation (ES) to peripheral nerves. ES acts through second messenger cyclic AMP to augment the intrinsic molecular pathways of regeneration. Decades of animal studies have demonstrated that 20 Hz ES delivered post-surgically accelerates axonal outgrowth and end organ reinnervation. This work has been translated clinically in a series of randomized clinical trials, which suggest that ES can be used as an efficacious therapy to improve patient outcomes following PNIs. The aim of this review is to discuss the cellular physiology and the limitations of regeneration after peripheral nerve injuries. The proposed mechanisms of ES protocols and how they facilitate nerve regeneration depending on timing of administration are outlined. Finally, future directions of research that may provide new perspectives on the optimal delivery of ES following PNI are discussed.

Recovering the regenerative potential in chronically injured nerves by using conditioning electrical stimulation.

OBJECTIVE: Chronically injured nerves pose a significant clinical challenge despite surgical management. There is no clinically feasible perioperative technique to upregulate a proregenerative environment in a chronic nerve injury. Conditioning electrical stimulation (CES) significantly improves sensorimotor recovery following acute nerve injury to the tibial and common fibular nerves. The authors' objective was to determine if CES could foster a proregenerative environment following chronically injured nerve reconstruction. METHODS: The tibial nerve of 60 Sprague Dawley rats was cut, and the proximal ends were inserted into the hamstring muscles to prevent spontaneous reinnervation. Eleven weeks postinjury, these chronically injured animals were randomized, and half were treated with CES proximal to the tibial nerve cut site. Three days later, 24 animals were killed to evaluate the effects of CES on the expression of regeneration-associated genes at the cell body (n = 18) and Schwann cell proliferation (n = 6). In the remaining animals, the tibial nerve defect was reconstructed using a 10-mm isograft. Length of nerve regeneration was assessed 3 weeks postgrafting (n = 16), and functional recovery was evaluated weekly between 7 and 19 weeks of regeneration (n = 20). RESULTS: Three weeks after nerve isograft surgery, tibial nerves treated with CES prior to grafting had a significantly longer length of nerve regeneration (p < 0.01). Von Frey analysis identified improved sensory recovery among animals treated with CES (p < 0.01). Motor reinnervation, assessed by kinetics, kinematics, and skilled motor tasks, showed significant recovery (p < 0.05 to p < 0.001). These findings were supported by immunohistochemical quantification of motor endplate reinnervation (p < 0.05). Mechanisms to support the role of CES in reinvigorating the regenerative response were assessed, and it was demonstrated that CES increased the proliferation of Schwann cells in chronically injured nerves (p < 0.05). Furthermore, CES upregulated regeneration-associated gene expression to increase growth-associated protein-43 (GAP-43), phosphorylated cAMP response element binding protein (pCREB) at the neuronal cell bodies, and upregulated glial fibrillary acidic protein expression in the surrounding satellite glial cells (p < 0.05 to p < 0.001). CONCLUSIONS: Regeneration following chronic axotomy is impaired due to downregulation of the proregenerative environment generated following nerve injury. CES delivered to a chronically injured nerve influences the cell body and the nerve to re-upregulate an environment that accelerates axon regeneration, resulting in significant improvements in sensory and motor functional recovery. Percutaneous CES may be a preoperative strategy to significantly improve outcomes for patients undergoing delayed nerve reconstruction.

Conditioning Electrical Stimulation Accelerates Regeneration in Nerve Transfers.

OBJECTIVE: Compared to the upper limb, lower limb distal nerve transfer (DNT) outcomes are poor, likely due to the longer length of regeneration required. DNT surgery to treat foot drop entails rerouting a tibial nerve branch to the denervated common fibular nerve stump to reinnervate the tibialis anterior muscle for ankle dorsiflexion. Conditioning electrical stimulation (CES) prior to nerve repair surgery accelerates nerve regeneration and promotes sensorimotor recovery. We hypothesize that CES prior to DNT will promote nerve regeneration to restore ankle dorsiflexion. METHODS: One week following common fibular nerve crush, CES was delivered to the tibial nerve in half the animals, and at 2 weeks, all animals received a DNT. To investigate the effects of CES on nerve regeneration, a series of kinetic, kinematic, skilled locomotion, electrophysiologic, and immunohistochemical outcomes were assessed. The effects of CES on the nerve were investigated. RESULTS: CES-treated animals had significantly accelerated nerve regeneration (p < 0.001), increased walking speed, and improved skilled locomotion. The injured limb had greater vertical peak forces, with improved duty factor, near-complete recovery of braking, propulsive forces, and dorsiflexion (p < 0.01). Reinnervation of the tibialis anterior muscle was confirmed with nerve conduction studies and immunohistochemical analysis of the neuromuscular junction. Immunohistochemistry demonstrated that CES does not induce Wallerian degeneration, nor does it cause macrophage infiltration of the distal tibial nerve. INTERPRETATION: Tibial nerve CES prior to DNT significantly improved functional recovery of the common fibular nerve and its muscle targets without inducing injury to the donor nerve. ANN NEUROL 2020;88:363-374.

Conditioning Electrical Stimulation Is Superior to Postoperative Electrical Stimulation in Enhanced Regeneration and Functional Recovery Following Nerve Graft Repair.

Background. Autologous nerve graft is the most common clinical intervention for repairing a nerve gap. However, its regenerative capacity is decreased in part because, unlike a primary repair, the regenerating axons must traverse 2 repair sites. Means to promote nerve regeneration across a graft are needed. Postoperative electrical stimulation (PES) improves nerve growth by reducing staggered regeneration at the coaptation site whereas conditioning electrical stimulation (CES) accelerates axon extension. In this study, we directly compared these electrical stimulation paradigms in a model of nerve autograft repair. Methods. To lay the foundation for clinical translation, regeneration and reinnervation outcomes of CES and PES in a 5-mm nerve autograft model were compared. Sprague-Dawley rats were divided into: (a) CES, (b) PES, and (c) no stimulation cohorts. CES was delivered 1 week prior to nerve cut/coaptation, and PES was delivered immediately following coaptation. Length of nerve regeneration (n = 6/cohort), and behavioral testing (n = 16/cohort) were performed at 14 days and 6 to 14 weeks post-coaptation, respectively. Results. CES treated axons extended 5.9 ± 0.2 mm, significantly longer than PES (3.8 ± 0.2 mm), or no stimulation (2.5 ± 0.2 mm) (P < .01). Compared with PES animals, the CES animals had significantly improved sensory recovery (von Frey filament testing, intraepidermal nerve fiber reinnervation) (P < .001) and motor reinnervation (horizontal ladder, gait analysis, nerve conduction studies, neuromuscular junction analysis) (P < .01). Conclusion. CES resulted in faster regeneration through the nerve graft and improved sensorimotor recovery compared to all other cohorts. It is a promising treatment to improve outcomes in patients undergoing nerve autograft repair.

Late animation deformity in the denervated pedicled latissimus dorsi flap.

Optimal management of the thoracodorsal nerve in pedicled latissimus dorsi flaps for mastectomy reconstruction is controversial. The incidence and etiology of animation deformity despite muscle denervation remain poorly- understood. This study examines the incidence, etiology, and risk factors of late animation. A retrospective review identified breasts reconstructed with a denervated pedicled latissimus dorsi flap. The incidence and severity of postoperative animation were examined with investigation of potential patient, oncologic, and reconstructive causative factors. Patients completed a survey to assess lifestyle implications. A cadaveric dissection identified anatomical causes of persistent muscle innervation. Forty-one reconstructions with a minimum follow-up of 2 years (average 6.25 years) identified no significant relationship between animation and patient or treatment factors. While absent in the first postoperative year, animation was identified in 90% of patients on long-term follow-up, with 32% reporting pain, and 25% indicating lifestyle interferences. This high frequency of animation correlated with cadaveric results that identified multiple extramuscular nerve branches innervating the latissimus in 9 of 10 specimens. The distance between nerve branches was 5.4 ± 0.7 mm, and the distance between the superior muscle margin and the branching point was 22.7 ± 2.3 mm. Persistent animation deformity, despite nerve transection, is attributable to anatomical differences in the thoracodorsal branching patterns, rather than patient or therapeutic factors. While early follow-up may suggest transection of a single nerve branch is adequate to prevent animation, our study demonstrates that long term, it is insufficient in most cases. Exploration for additional nerve branches or high division proximal to the branching site is suggested, and preoperative patient counseling is recommended.

Conditioning electrical stimulation is superior to postoperative electrical stimulation, resulting in enhanced nerve regeneration and functional recovery.

Postoperative electrical stimulation (PES) improves nerve regeneration by decreasing staggered regeneration at the coaptation site. By contrast, conditioning (preoperative) electrical stimulation (CES) accelerates axon extension. Given that both techniques can be delivered at the bedside, a direct comparison of outcomes is of significant clinical importance. In this study, we compared regeneration and reinnervation outcomes of CES, PES, a combination of CES and PES, and a no stimulation control. Sprague Dawley rats were randomly divided into i) CES, ii) PES, iii) CES + PES, and iv) no stimulation. CES was delivered one week prior to nerve cut/coaptation, and PES was delivered immediately following nerve repair. Length of nerve regeneration was assessed at 7 days post-coaptation (n = 6/cohort), and behavioral testing was performed between 6 and 8 weeks post-coaptation (n = 8/cohort). Animals treated with CES had significantly longer axon extension and improved sensorimotor recovery compared to all other cohorts. CES treated axons extended 8.5 ± 0.6 mm, significantly longer than PES (5.5 ± 0.5 mm), CES + PES (3.6 ± 0.7 mm), or no stimulation (2.7 ± 0.5 mm) (p < .001). Sensory recovery (von Frey filament testing, intraepidermal nerve fiber reinnervation) (p < .001) and motor reinnervation (horizontal ladder, gait analysis, nerve conduction studies, neuromuscular junction analysis) (p < .05 - p < .001) were significantly improved in CES animals. CES significantly improves regeneration and reinnervation beyond the current clinical paradigm of PES. The combination of CES and PES does not have a synergistic effect. CES alone therefore may be a more promising treatment to improve outcomes in patients undergoing nerve repair surgeries.

Conditioning electrical stimulation promotes functional nerve regeneration.

Peripheral nerve regeneration following injury is often incomplete, resulting in significant personal and socioeconomic costs. Although a conditioning crush lesion prior to surgical nerve transection and repair greatly promotes nerve regeneration and functional recovery, feasibility and ethical considerations have hindered its clinical applicability. In a recent proof of principle study, we demonstrated that conditioning electrical stimulation (CES) had effects on early nerve regeneration, similar to that seen in conditioning crush lesions (CCL). To convincingly determine its clinical utility, establishing the effects of CES on target reinnervation and functional outcomes is of utmost importance. In this study, we found that CES improved nerve regeneration and reinnervation well beyond that of CCL. Specifically, compared to CCL, CES resulted in greater intraepidermal skin and NMJ reinnervation, and greater physiological and functional recovery including mechanosensation, compound muscle action potential on nerve conduction studies, normalization of gait pattern, and motor performance on the horizontal ladder test. These findings have direct clinical relevance as CES could be delivered at the bedside before scheduled nerve surgery.

The nerve conditioning lesion: A strategy to enhance nerve regeneration.

By altering the intrinsic metabolism of the cell, including the upregulation of regeneration-associated genes (RAGs) and the production of structural proteins for axonal outgrowth, the conditioning lesion sets up an environment highly conducive to regeneration. In this review, we assess 40 years of research to provide a comprehensive overview of the conditioning lesion literature, directed at (1) discussing the mechanisms of and barriers to nerve regeneration that can be mitigated by the conditioning lesion, (2) describing the cellular and molecular pathways implicated in the conditioning lesion effect, and (3) deliberating on how these insights might be applied clinically. The consequential impact on regeneration is profound, with a conditioned nerve demonstrating longer neurite extensions in vitro, enhanced expression of RAGs within the dorsal root ganglia, early assembly and transportation of cytoskeletal elements, accelerated axonal growth, and improved functional recovery in vivo. Although this promising technique is not yet feasible to be performed in humans, there are potential strategies, such as conditioning electrical stimulation that may be explored to allow nerve conditioning in a clinically safe and well-tolerated manner. Ann Neurol 2018;83:691-702.

Invasive lobular carcinoma of the male breast - a systematic review with an illustrative case study.

Male breast cancer is rare, comprising only 1% of all mammary cancers; invasive ductal carcinoma is by far the commonest subtype in both men and women. Though lobular breast cancer is the second most common subtype seen in women, such cancers are extremely uncommon in men, and this is likely related to the lack of lobular development in the male breast. Thus, due to the rarity of this subtype among breast cancers, compounded by the overall rarity of breast cancer in men, current understanding of the pathogenesis of this disease and its management is largely derived from case series and extrapolation of information from the larger cohort of female patients. This paper provides a systematic review on invasive lobular carcinoma of the male breast in the context of an illustrative case study. A comprehensive analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results Data 1973-2013 leading to an exploration of the pathogenesis, epidemiology, clinical presentation, diagnosis, tumor characteristics, and management of lobular breast carcinoma in men is also discussed. Lobular subtype of breast cancer remains an enigmatic elusive disease that needs additional research to unravel its overall pathogenesis and molecular profile to provide insight for improved therapeutic management options.

Gastric biomarkers: a global review.

BACKGROUND: Gastric cancer is an aggressive disease with a poor 5-year survival and large global burden of disease. The disease is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Despite the many prognostic, predictive, and therapeutic biomarkers investigated to date, gastric cancer continues to be detected at an advanced stage with resultant poor clinical outcomes. MAIN BODY: This is a global review of gastric biomarkers with an emphasis on HER2, E-cadherin, fibroblast growth factor receptor, mammalian target of rapamycin, and hepatocyte growth factor receptor as well as sections on microRNAs, long noncoding RNAs, matrix metalloproteinases, PD-L1, TP53, and microsatellite instability. CONCLUSION: A deeper understanding of the pathogenesis and biological features of gastric cancer, including the identification and characterization of diagnostic, prognostic, predictive, and therapeutic biomarkers, hopefully will provide improved clinical outcomes.

Gallbladder Cancer in the 21st Century.

Gallbladder cancer (GBC) is an uncommon disease in the majority of the world despite being the most common and aggressive malignancy of the biliary tree. Early diagnosis is essential for improved prognosis; however, indolent and nonspecific clinical presentations with a paucity of pathognomonic/predictive radiological features often preclude accurate identification of GBC at an early stage. As such, GBC remains a highly lethal disease, with only 10% of all patients presenting at a stage amenable to surgical resection. Among this select population, continued improvements in survival during the 21st century are attributable to aggressive radical surgery with improved surgical techniques. This paper reviews the current available literature of the 21st century on PubMed and Medline to provide a detailed summary of the epidemiology and risk factors, pathogenesis, clinical presentation, radiology, pathology, management, and prognosis of GBC.

Fibrolipomatous hamartoma of the median nerve: A cause of acute bilateral carpal tunnel syndrome in a three-year-old child: A case report and comprehensive literature review.

A three-year-old boy was investigated for inexplicable incessant crying. On examination, his left wrist was mildly swollen (three to four months) and sensitive. Exploration and carpal tunnel decompression of the left wrist with incisional biopsy was performed for the presence of a fusiform swelling intimately associated with the median nerve. Histopathology revealed the presence of enlarged nerve bundles admixed with mature fat cells and diffuse fibroblastic proliferation. Three months later, he underwent urgent contralateral carpal tunnel decompression for a similar presentation. The final diagnosis was bilateral fibrolipomatous hamartoma (FLH) of the median nerves causing acute bilateral compression neuropathy. FLH of the median nerve is an extremely unusual cause of acute bilateral carpal tunnel syndrome in a young child presenting with 'incessant crying'. A comprehensive review of FLH including epidemiology, etiology, clinical presentation, differential diagnosis, imaging, pathology, treatment and prognosis is discussed.

Un enfant de trois ans a subi des examens en raison de pleurs incessants inexplicables. À l'examen, son poignet gauche était légèrement enflé (depuis trois ou quatre mois) et sensible. Une exploration, suivie d'une décompression du tunnel carpien du poignet gauche par biopsie incisionnelle ont été effectuées pour établir la présence d'œdème fusiforme intimement associé au nerf médian. L'histopathologie a révélé une hypertrophie du faisceau nerveux mêlée à des cellules adipeuses matures et à une prolifération fibroblasique diffuse. Trois mois plus tard, l'enfant a subi une décompression controlatérale urgente du tunnel du canal carpien dans une présentation similaire. Le diagnostic final était un hamartome fibrolipomateux (HFL) bilatéral des nerfs médians responsable d'une neuropathie de compression bilatérale aiguë.L'HFL du nerf médian est une cause extrêmement inhabituelle de syndrome du canal carpien aigu bilatéral chez un jeune enfant qui « pleurait constamment ¼. Une analyse complète de l'HFL est exposée, incluant l'épidémiologie, l'étiologie, la présentation clinique, le diagnostic différentiel, l'imagerie, la pathologie, le traitement et le pronostic.

Is routine pathological evaluation of tissue from gynecomastia necessary? A 15-year retrospective pathological and literature review.

OBJECTIVE: To reconsider the routine plastic surgical practice of requesting histopathological evaluation of tissue from gynecomastia. METHOD: The present study was a retrospective histopathological review (15-year period [1996 to 2012]) involving gynecomastia tissue samples received at the pathology laboratory in the Saskatoon Health Region (Saskatchewan). The Laboratory Information System (LIS) identified all specimens using the key search words "gynecomastia", "gynaecomastia", "gynecomazia" and "gynaecomazia". A literature review to identify all cases of incidentally discovered malignancies in gynecomastia tissue specimens over a 15-year period (1996 to present) was undertaken. RESULTS: The 15-year LIS search detected a total of 452 patients that included two cases of pseudogynecomastia (0.4%). Patients' age ranged from five to 92 years and 43% of the cases were bilateral (28% left sided, 29% right sided). The weight of the specimens received ranged from 0.2 g to 1147.2 g. All cases showed no significant histopathological concerns. The number of tissue blocks sampled ranged from one to 42, averaging four blocks/case (approximately $105/case), resulting in a cost of approximately $3,200/year, with a 15-year expenditure of approximately $48,000. The literature review identified a total of 15 incidental findings: ductal carcinoma in situ (12 cases), atypical ductal hyperplasia (two cases) and infiltrating ductal carcinoma (one case). CONCLUSIONS: In the context of evidence-based literature, and because no significant pathological findings were detected in this particular cohort of 452 cases with 2178 slides, the authors believe it is time to re-evaluate whether routine histopathological examination of tissue from gynecomastia remains necessary. The current climate of health care budget fiscal restraints warrants reassessment of the current policies and practices of sending tissue samples of gynecomastia incurring negative productivity costs on routine histopathological examination.

OBJECTIF: Revoir la pratique chirurgicale systématique qui consiste à demander une évaluation histopathologique des tissus de gynécomastie. MÉTHODOLOGIE: La présente analyse histopathologique rétrospective (sur 15 ans [1996 à 2012]) portait sur les prélèvements de tissus de gynécomastie reçus au laboratoire de pathologie de la Régie régionale de la santé de Saskatoon, en Saskatchewan. Le Système d'information de laboratoire (SIL) a répertorié tous les prélèvements au moyen des mots-clés gynecomastia, gynaecomastia, gynecomazia et gynaecomazia. Une analyse bibliographique a permis de repérer tous les cas de cancers découverts fortuitement dans des prélèvements de tissu de gynécomastie sur une période de 15 ans (1996 à maintenant). RÉSULTATS: La recherche du SIL sur 15 ans a décelé un total de 452 patients, dont deux cas de pseudogynécomastie (0,4 %). Les patients avaient de cinq à 92 ans, et 43 % des cas étaient bilatéraux (28 % du côté gauche, 29 % du côté droit). Le poids des prélèvements reçus variait entre 0,2 g et 1 147,2 g. Aucun cas ne suscitait de préoccupations histopathologiques. De un à 42 blocs de tissu avaient été prélevés, pour une moyenne de quatre blocs par cas (environ 105 $ par cas) et un coût d'environ 3 200 $ par année, ce qui correspond à des dépenses d'environ 48 000 $ sur 15 ans. L'analyse bibliographique a permis de repérer un total de 15 observations fortuites : carcinome canalaire in situ (12 cas), hyperplasie canalaire atypique (deux cas) et carcinome canalaire infiltrant (un cas). CONCLUSIONS: Compte tenu des publications fondées sur des données probantes et de l'absence d'observations pathologiques significatives au sein de cette cohorte de 452 cas associés à 2 178 lames, les auteurs pensent qu'il est temps de réévaluer la nécessité des examens histopathologiques systématiques des tissus de gynécomastie. Dans le climat actuel de compressions budgétaires dans le domaine de la santé, il est justifié de réévaluer les politiques et pratiques actuelles consistant à envoyer des échantillons de tissus de gynécomastie qui nuisent aux coûts de productivité de l'examen histopathologique systématique.

Fecal molecular markers for colorectal cancer screening.

Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.

The multifaceted granulosa cell tumours-myths and realities: a review.

Background. Granulosa cell tumors (GCTs), representing ~2% of ovarian tumours, are poorly understood neoplasms with unpredictable and undetermined biological behaviour. Design. 5 unusual presentations of GCT and a retrospective 14-year (1997-2011) surgical pathology review based on patient sex, age, tumour type and concurrent pathology findings are presented to discuss the "myths and realities" of GCTs in the context of relevant evidence-based literature. Results. The 5 index cases included (1) a 5 month-old boy with a left testicular mass, (2) a 7-day-old neonate with a large complex cystic mass in the abdomen, (3) a 76-year-old woman with an umbilical mass, (4) a 64-year-old woman with a complex solid-cystic pelvic mass, and (5) a 45 year-old woman with an acute abdomen. Pathological analysis confirmed the final diagnosis as (1) juvenile GCT, (2) macrofollicular GCT, (3) recurrent GCT 32 years later, (4) collision tumour: colonic adenocarcinoma and GCT, and (5) ruptured GCT. Conclusion. GCT is best considered as an unusual indolent neoplasm of low malignant potential with late recurrences that can arise in the ovaries and testicles in both the young and the old. Multifaceted clinical presentations coupled with the unpredictable biological behaviour with late relapses are diagnostic pitfalls necessitating a high degree of suspicion for accurate clinical and pathological diagnosis.